Germline variation at 8q24 and prostate cancer risk in men of European ancestry

Marco Matejcic; Edward J. Saunders; Tokhir Dadaev; Mark N. Brook; Kan Wang; Xin Sheng; Ali Amin Al Olama; Fredrick R. Schumacher; Sue A. Ingles; Koveela Govindasami; Sara Benlloch; Sonja I. Berndt; Demetrius Albanes; Stella Koutros; Kenneth Muir; Victoria L. Stevens; Susan M. Gapstur; Catherine M. Tangen; Jyotsna Batra; Judith Clements; Henrik Gronberg; Nora Pashayan; Johanna Schleutker; Alicja Wolk; Catharine West; Lorelei Mucci; Peter Kraft; Géraldine Cancel-Tassin; Karina D. Sorensen; Lovise Maehle; Eli M. Grindedal; Sara S. Strom; David E. Neal; Freddie C. Hamdy; Jenny L. Donovan; Ruth C. Travis; Robert J. Hamilton; Barry Rosenstein; Yong Jie Lu; Graham G. Giles; Adam S. Kibel; Ana Vega; Jeanette T. Bensen; Manolis Kogevinas; Kathryn L. Penney; Jong Y. Park; Janet L. Stanford; Cezary Cybulski; Børge G. Nordestgaard; Hermann Brenner; PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium

doi:10.1038/s41467-018-06863-1

Germline variation at 8q24 and prostate cancer risk in men of European ancestry

Marco Matejcic, Edward J. Saunders, Tokhir Dadaev, Mark N. Brook, Kan Wang, Xin Sheng, Ali Amin Al Olama, Fredrick R. Schumacher, Sue A. Ingles, Koveela Govindasami, Sara Benlloch, Sonja I. Berndt, Demetrius Albanes, Stella Koutros, Kenneth Muir, Victoria L. Stevens, Susan M. Gapstur, Catherine M. Tangen, Jyotsna Batra, Judith ClementsHenrik Gronberg, Nora Pashayan, Johanna Schleutker, Alicja Wolk, Catharine West, Lorelei Mucci, Peter Kraft, Géraldine Cancel-Tassin, Karina D. Sorensen, Lovise Maehle, Eli M. Grindedal, Sara S. Strom, David E. Neal, Freddie C. Hamdy, Jenny L. Donovan, Ruth C. Travis, Robert J. Hamilton, Barry Rosenstein, Yong Jie Lu, Graham G. Giles, Adam S. Kibel, Ana Vega, Jeanette T. Bensen, Manolis Kogevinas, Kathryn L. Penney, Jong Y. Park, Janet L. Stanford, Cezary Cybulski, Børge G. Nordestgaard, Hermann Brenner, PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium

Department of Clinical Medicine

21 Citations (Scopus)

38 Downloads (Pure)

Abstract

Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10⁻¹⁵), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification.

Original language	English
Article number	4616
Journal	Nature Communications
Volume	9
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-018-06863-1
Publication status	Published - 1 Dec 2018

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41467-018-06863-1Licence: CC BY

Germline variation at 8q24 and prostate cancer risk in men of European ancestryFinal published version, 1.58 MBLicence: CC BY

Cite this

Matejcic, M., Saunders, E. J., Dadaev, T., Brook, M. N., Wang, K., Sheng, X., Olama, A. A. A., Schumacher, F. R., Ingles, S. A., Govindasami, K., Benlloch, S., Berndt, S. I., Albanes, D., Koutros, S., Muir, K., Stevens, V. L., Gapstur, S. M., Tangen, C. M., Batra, J., ... PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium (2018). Germline variation at 8q24 and prostate cancer risk in men of European ancestry. Nature Communications, 9, [4616]. https://doi.org/10.1038/s41467-018-06863-1

Matejcic, M, Saunders, EJ, Dadaev, T, Brook, MN, Wang, K, Sheng, X, Olama, AAA, Schumacher, FR, Ingles, SA, Govindasami, K, Benlloch, S, Berndt, SI, Albanes, D, Koutros, S, Muir, K, Stevens, VL, Gapstur, SM, Tangen, CM, Batra, J, Clements, J, Gronberg, H, Pashayan, N, Schleutker, J, Wolk, A, West, C, Mucci, L, Kraft, P, Cancel-Tassin, G, Sorensen, KD, Maehle, L, Grindedal, EM, Strom, SS, Neal, DE, Hamdy, FC, Donovan, JL, Travis, RC, Hamilton, RJ, Rosenstein, B, Lu, YJ, Giles, GG, Kibel, AS, Vega, A, Bensen, JT, Kogevinas, M, Penney, KL, Park, JY, Stanford, JL, Cybulski, C, Nordestgaard, BG, Brenner, H & PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium 2018, 'Germline variation at 8q24 and prostate cancer risk in men of European ancestry', Nature Communications, vol. 9, 4616. https://doi.org/10.1038/s41467-018-06863-1

@article{10e71316fd4f4427841a6ca44e3e82c3,

title = "Germline variation at 8q24 and prostate cancer risk in men of European ancestry",

abstract = "Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10−15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification.",

author = "Marco Matejcic and Saunders, {Edward J.} and Tokhir Dadaev and Brook, {Mark N.} and Kan Wang and Xin Sheng and Olama, {Ali Amin Al} and Schumacher, {Fredrick R.} and Ingles, {Sue A.} and Koveela Govindasami and Sara Benlloch and Berndt, {Sonja I.} and Demetrius Albanes and Stella Koutros and Kenneth Muir and Stevens, {Victoria L.} and Gapstur, {Susan M.} and Tangen, {Catherine M.} and Jyotsna Batra and Judith Clements and Henrik Gronberg and Nora Pashayan and Johanna Schleutker and Alicja Wolk and Catharine West and Lorelei Mucci and Peter Kraft and G{\'e}raldine Cancel-Tassin and Sorensen, {Karina D.} and Lovise Maehle and Grindedal, {Eli M.} and Strom, {Sara S.} and Neal, {David E.} and Hamdy, {Freddie C.} and Donovan, {Jenny L.} and Travis, {Ruth C.} and Hamilton, {Robert J.} and Barry Rosenstein and Lu, {Yong Jie} and Giles, {Graham G.} and Kibel, {Adam S.} and Ana Vega and Bensen, {Jeanette T.} and Manolis Kogevinas and Penney, {Kathryn L.} and Park, {Jong Y.} and Stanford, {Janet L.} and Cezary Cybulski and Nordestgaard, {B{\o}rge G.} and Hermann Brenner and {PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium}",

year = "2018",

month = dec,

day = "1",

doi = "10.1038/s41467-018-06863-1",

language = "English",

volume = "9",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "nature publishing group",

}

TY - JOUR

T1 - Germline variation at 8q24 and prostate cancer risk in men of European ancestry

AU - Matejcic, Marco

AU - Saunders, Edward J.

AU - Dadaev, Tokhir

AU - Brook, Mark N.

AU - Wang, Kan

AU - Sheng, Xin

AU - Olama, Ali Amin Al

AU - Schumacher, Fredrick R.

AU - Ingles, Sue A.

AU - Govindasami, Koveela

AU - Benlloch, Sara

AU - Berndt, Sonja I.

AU - Albanes, Demetrius

AU - Koutros, Stella

AU - Muir, Kenneth

AU - Stevens, Victoria L.

AU - Gapstur, Susan M.

AU - Tangen, Catherine M.

AU - Batra, Jyotsna

AU - Clements, Judith

AU - Gronberg, Henrik

AU - Pashayan, Nora

AU - Schleutker, Johanna

AU - Wolk, Alicja

AU - West, Catharine

AU - Mucci, Lorelei

AU - Kraft, Peter

AU - Cancel-Tassin, Géraldine

AU - Sorensen, Karina D.

AU - Maehle, Lovise

AU - Grindedal, Eli M.

AU - Strom, Sara S.

AU - Neal, David E.

AU - Hamdy, Freddie C.

AU - Donovan, Jenny L.

AU - Travis, Ruth C.

AU - Hamilton, Robert J.

AU - Rosenstein, Barry

AU - Lu, Yong Jie

AU - Giles, Graham G.

AU - Kibel, Adam S.

AU - Vega, Ana

AU - Bensen, Jeanette T.

AU - Kogevinas, Manolis

AU - Penney, Kathryn L.

AU - Park, Jong Y.

AU - Stanford, Janet L.

AU - Cybulski, Cezary

AU - Nordestgaard, Børge G.

AU - Brenner, Hermann

AU - PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10−15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification.

AB - Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10−15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification.

UR - https://www.nature.com/articles/s41467-019-08293-z

U2 - 10.1038/s41467-018-06863-1

DO - 10.1038/s41467-018-06863-1

M3 - Journal article

C2 - 30397198

AN - SCOPUS:85056250910

SN - 2041-1723

VL - 9

JO - Nature Communications

JF - Nature Communications

M1 - 4616

ER -

Germline variation at 8q24 and prostate cancer risk in men of European ancestry

Abstract

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this